TY - JOUR
T1 - Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease
AU - Sintini, Irene
AU - Schwarz, Christopher G.
AU - Martin, Peter R.
AU - Graff-Radford, Jonathan
AU - Machulda, Mary M.
AU - Senjem, Matthew L.
AU - Reid, Robert I.
AU - Spychalla, Anthony J.
AU - Drubach, Daniel A.
AU - Lowe, Val J.
AU - Jack, Clifford R.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Funding Information:
information National Institutes of Health, Grant/Award Numbers: U01-AG006786, R21-NS94684, R01-AG50603This work was supported by the National Institutes of Health (grant numbers R01-AG50603, R21-NS94684, U01-AG006786). We would like to acknowledge Dr. Ronald Petersen and Dr. David Knopman for collecting the control subjects. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying the AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work. Disclosures outside the submitted work: M.L.S. owns stocks in Align Technology, Inc., Gilead Sciences, Globus Medical Inc., Inovio Biomedical Corp., Johnson & Johnson, LHC Group, Inc., Medtronic, Inc., Mesa Laboratories, Inc., Natus Medical Incorporated, Oncothyreon, Inc., Parexel International Corporation, and Varex Imaging Corporation. V.J.L. consults for Bayer Schering Pharma, Piramal Life Sciences, and receives grants from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals.
Funding Information:
This work was supported by the National Institutes of Health (grant numbers R01-AG50603, R21-NS94684, U01-AG006786). We would like to acknowledge Dr. Ronald Petersen and Dr. David Knopman for collecting the control subjects. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying the AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [ 18 F]fluorodeoxyglucose (FDG) PET, tau uptake on [ 18 F]AV-1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region- and voxel-level. Forty atypical AD patients underwent MRI, FDG-PET, tau-PET, beta-amyloid PET, and DTI. Patients were all beta-amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI-volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel-level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI-volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.
AB - Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [ 18 F]fluorodeoxyglucose (FDG) PET, tau uptake on [ 18 F]AV-1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region- and voxel-level. Forty atypical AD patients underwent MRI, FDG-PET, tau-PET, beta-amyloid PET, and DTI. Patients were all beta-amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI-volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel-level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI-volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.
KW - DTI
KW - FDG
KW - MRI
KW - atypical Alzheimer's disease
KW - multimodal imaging
KW - multivariate analysis
KW - tau
UR - http://www.scopus.com/inward/record.url?scp=85058384555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058384555&partnerID=8YFLogxK
U2 - 10.1002/hbm.24473
DO - 10.1002/hbm.24473
M3 - Article
C2 - 30549156
AN - SCOPUS:85058384555
VL - 40
SP - 1618
EP - 1631
JO - Human Brain Mapping
JF - Human Brain Mapping
SN - 1065-9471
IS - 5
ER -